Proton-pump inhibitors (PPIs) are the most effective therapy for the full spectrum of gastric-acid-related diseases. However, in the past decade, a steadily increasing list of complications following ...long-term use of PPIs has been reported. Their potent acid-suppressive action induces several structural and functional changes within the gastric mucosa, including fundic gland polyps, enterochromaffin-like cell hyperplasia and hypergastrinaemia, which can be exaggerated in the presence of Helicobacter pylori infection. As discussed in this Review, most associations of PPIs with severe adverse events are not based on sufficient evidence because of confounding factors and a lack of plausible mechanisms. Thus, a causal relationship remains unproven in most associations, and further studies are needed. Awareness of PPI-associated risks should not lead to anxiety in patients but rather should induce the physician to consider the appropriate dosing and duration of PPI therapy, including long-term monitoring strategies in selected groups of patients because of their individual comorbidities and risk factors.
Gastric cancer (GC) is still the third leading cause of cancer death in both sexes worldwide. Helicobacter pylori infection is the most important risk factor for GC and, in spite of the consistent ...trend of a decreasing incidence, in 2015 approximately 4.4 billion individuals—more than half the world's population—were infected with H. pylori. The birth cohort pattern of decreased H. pylori infection reported in a systematic review contributes to explain the declining GC mortality in Japan. Current trends in estimated annual percentage change of GC incidence foreshadow expected reversals in both falling incidence and male predominance among US non‐Hispanic whites. Combining serum pepsinogen 1 and H. pylori serology was shown to be useful for GC risk stratification in a Finnish population. Gastritis staging by operative link on gastritis assessment was confirmed to be reliable in predicting GC risk in a large prospective study. In a randomized trial from South Korea, H. pylori eradication therapy significantly reduced the rates of metachronous GC in patients who received curative endoscopic resection for early GC. A study based on a territory‐wide health care database of the Hong Kong Hospital Authority showed that aspirin use is associated with a reduced GC risk. Another study based on the same database showed that proton pump inhibitors increase GC risk, but methodological biases have most likely acted as confounders. Confirmatory data on the role of endoscopic submucosal dissection in patients with early GC have been published. The phase III FLOT4 trial has shown that the FLOT triplet regimen (docetaxel, oxaliplatin, leucovorin, and 5‐fluorouracil) improves the outcome of patients with GC and locoregional disease as compared to the ECF triplet (epirubicin, cisplatin, and 5‐fluorouracil). In the phase III ATTRACTION‐2 trial, nivolumab was shown to be an effective treatment option with a relative safe profile for heavily pretreated patients with advanced GC.
Gastric cancer (GC) was responsible for over 1 000 000 new cases in 2018 and an estimated 783 000 deaths, making it still the fifth most frequently diagnosed cancer and the third leading cause of ...cancer deaths in both sexes worldwide. Divergent trends for GC incidence were observed in the USA. Incidence rates, particularly for non‐cardia GC, were stable or increasing among persons aged <50 years. In an analysis of data from a public hospital database in Hong Kong, treatment of Helicobacter pylori infection was associated with a lower risk of GC, particularly in older subjects who received treatment ≥10 years before. Based on the results of a 16‐year endoscopy‐based follow‐up eradication trial, patients with incomplete‐type intestinal metaplasia (IM) should receive endoscopic surveillance upon H. pylori eradication therapy. Updated guidelines on the endoscopic surveillance of preneoplastic conditions of the stomach (MAPS II) have been published. In the RAINFALL trial, the addition of ramucirumab to a backbone chemotherapy as a first‐line regimen failed to improve overall survival (OS) of patients with metastatic disease. Also, pembrolizumab did not prolong OS when compared to paclitaxel in the second‐line treatment of patients with advanced GC or esophagogastric junction (EGJ) cancer. Trifluridine/tipiracil improved OS by 2.1 months in the third or further treatment line of patients with advanced GC. In a systematic investigation conducted on Chinese patients with GC, CLDN18‐ARHGAP26/6 fusion was associated with signet‐ring cell content and was prognostic for a worse outcome and predictive for no benefit from oxaliplatin/fluoropyrimidine‐based chemotherapy. Organoid cultures represent an appealing model that may be applied for therapy response testing in the near future.
Background and Objectives
S-1-based regimens have been shown to be as effective as other fluoropyrimidine-based regimens with a better safety profile in patients with advanced esophagogastric ...adenocarcinoma. However, real-world data on S-1 in European patients with advanced esophagogastric adenocarcinoma are lacking. The Safety Compliance Observatory on Oral fluoroPyrimidines (SCOOP) study evaluated safety and relative dose intensities for patients treated with S-1-based regimens for advanced esophagogastric adenocarcinoma as part of daily practice.
Methods
Overall, data for 125 patients with advanced esophagogastric adenocarcinoma were collected at 21 centers in five countries in Europe. Demographics, treatment, and adverse-event data were recorded over a planned treatment of six cycles.
Results
Most patients (87%) received combination treatment of S-1 plus a platinum compound. Adverse events related to S-1 treatment were mostly grade 1 or 2 while reported grade 3–4 serious adverse events related to S-1 occurred in 12 patients and were most often grade 3 neutropenia (
n
= 4, 3.2%) or diarrhea (
n
= 5, 4%). The most common adverse events of any grade that were attributable to S-1 treatment included neutropenia, anemia, thrombocytopenia, diarrhea, nausea, vomiting, and fatigue. No patients experienced mucositis, dehydration, or febrile neutropenia, whereas 2% (3/125) of patients experienced hand-foot syndrome.
Conclusion
The overall relative dose intensity was 70%. In a real-world setting, patients with advanced esophagogastric adenocarcinoma tolerated S-1 treatment well with high compliance rates. The SCOOP study provides valuable information on S-1 relative dose intensity that can be used for treatment decision making.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Review: Prevention and management of gastric cancer Venerito, Marino; Ford, Alexander C.; Rokkas, Theodoros ...
Helicobacter (Cambridge, Mass.),
September 2020, 2020-09-00, 20200901, Letnik:
25, Številka:
S1
Journal Article
Recenzirano
Odprti dostop
Gastric cancer (GC) is still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Although the incidence of GC is predicted to continue ...declining in a growing number of countries in the future, on a global scale the number of newly diagnosed GC cases will remain high, or increase even further, due to changes in population size and increasing risks observed in younger generations. In a retrospective cohort study, collecting data from the Veterans Health Administration, treatment of Helicobacter pylori infection decreased GC risk only if eradication was successful. In a German case‐control study, among GC patients with autoimmune gastritis, pernicious anemia was associated with earlier detection of GC, which translated into a significantly better 5‐year survival. In an updated meta‐analysis, H. pylori eradication therapy in healthy individuals significantly reduced both GC incidence and mortality from GC with a number needed to treat of 72 and 135, respectively. In Korea, successful H. pylori eradication substantially reduced GC incidence in first‐degree relatives of GC patients as well. A meta‐analysis of four trials including 1,556 patients with resectable GC reported that the patient subgroup tumors with high microsatellite instability undergoing surgery did not benefit from perioperative or adjuvant chemotherapy.
In areas with high clarithromycin resistance, bismuth quadruple therapy (BQT) is recommended instead of clarithromycin triple therapy (CTT) as the first-line treatment for Helicobacter pylori ...eradication.
Randomized clinical trials (RCTs) comparing BQT to CTT were identified through electronic and manual searches. A meta-analysis was performed to compare the efficacy and tolerability of these two regimens as first-line treatments for H. pylori infection. The effect of antibiotic resistance on treatment efficacy was also analyzed.
Twelve RCTs were included. BQT achieved eradication in 77.6% of patients, whereas CTT achieved an eradication rate of 68.9% risk difference (RD) = 0.06, 95% CI: -0.01/0.13. A high heterogeneity among the trials was found (χ2 = 50.16, p < 0.00001; I2 = 78%). In the subgroup analysis for treatment duration, the 10-day BQT was more effective than the 7-day CTT (RD = 0.25, 95% CI: 0.18/0.32), whereas no differences were observed between CTT and BQT given for 7 or 10 days. There were no statistical differences in side effects and compliance between both therapies (RD = 0.92, 95% CI: 0.76/1.12, and RD = -0.03, 95% CI: -0.05/0.00, respectively). The effect of antibiotic resistance on eradication rates was reported in 4 of the 12 RCTs. Clarithromycin resistance significantly affected the efficacy of CTT (RD = 0.75, 95% CI: 0.63/0.87), whereas BQT efficacy was not affected by metronidazole resistance (RD = 0.09, 95% CI: -0.06/0.25).
The 10-day BQT was more effective than the 7-day CTT as a first-line therapy for H. pylori infection, whereas BQT and CTT for 7 or 10 days yielded similar eradication rates. Compliance and side effect rates were similar for both therapies. BQT overcomes clarithromycin resistance and its efficacy is not affected by metronidazole resistance.
In a retrospective study performed in California, U.S.A., ca. 3% of patients with gastric intestinal metaplasia (GIM) developed gastric cancer (GC) within a median time period of 4.6 years after ...diagnosis of GIM. This observation stresses the importance of targeted surveillance even in regions with a low GC prevalence. Patients with alcoholic liver disease as well as survivors of colorectal and lobular breast cancer were found to be at increased risk of secondary GC. A population‐based Chinese study confirmed “serologic biopsy” as a useful screening tool for stratifying the individual risk of developing GC. Concerning GC therapy, a post hoc analysis of the MAGIC trial reported that regression of lymph node metastases, but not the tumor regression itself, predicts overall survival. Furthermore, in patients with high microsatellite instable tumors, perioperative chemotherapy leads to an increased risk of mortality. Two studies confirmed that eradication therapy is worthwhile as an initial treatment for gastric mucosa‐associated lymphoid tissue (MALT) lymphoma irrespective of the H. pylori infection status and stage. An increased risk of a second primary malignancy including GC was observed in these patients treated with immuno/chemotherapy but not in patients treated solely with an H. pylori eradication treatment. With respect to gastrointestinal malignancies other than GC, discrepant data have been published regarding the association of H. pylori with pancreatic cancer whereas no association has been reported with esophageal squamous cell carcinoma. The majority of published studies still support an association of H. pylori with colon neoplasms.
The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the ...frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the "European Registry on Helicobacter pylori management."
Systematic prospective noninterventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control.
The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies.
Helicobacter pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment compliance.
Background
Autoimmune atrophic gastritis (AAG) is a chronic disease that can progress to gastric cancer (GC). To better understand AAG pathology, this proteomics study investigated gastric proteins ...whose expression levels are altered in this disease and also in GC.
Methods
Using two-dimensional difference gel electrophoresis (2D-DIGE), we compared protein maps of gastric corpus biopsies from AAG patients and controls. Differentially abundant spots (|fold change|≥ 1.5,
P
< 0.01) were selected and identified by LC–MS/MS. The spots were further assessed in gastric antrum biopsies from AAG patients (without and with
Helicobacter pylori
infection) and from GC patients and unaffected first-degree relatives of GC patients.
Results
2D-DIGE identified 67 differentially abundant spots, with 28 more and 39 less abundant in AAG-corpus than controls. LC–MS/MS identified these as 53 distinct proteins. The most significant (adjusted
P
< 0.01) biological process associated with the less abundant proteins was “tricarboxylic acid cycle”. Of the 67 spots, 57 were similarly differentially abundant in AAG-antrum biopsies irrespective of
H. pylori
infection status. The differential abundance was also observed in GC biopsies for 14 of 28 more abundant and 35 of 39 less abundant spots, and in normal gastric biopsies of relatives of GC patients for 6 and 25 spots, respectively. Immunoblotting confirmed the different expression levels of two more abundant proteins (
PDIA3, GSTP
gene products) and four less abundant proteins (
ATP5F1A, PGA3, SDHB, PGC
).
Conclusion
This study identified a proteomics signature of AAG. Many differential proteins were shared by GC and may be involved in the progression of AAG to GC.
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